We have previously shown that human pre-invasive diseases of the breast are
angiogenic. In addition, normal epithelium from women with coincident or s
ubsequent invasive breast cancer is more vascular than normal epithelium fr
om women with no breast cancer. To develop a model in which to study the re
gulation of angiogenesis in pre-invasive mammary pathologies, we examined 7
,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tissues for the pr
esence of neovascularization in pre-invasive histopathologies. These studie
s included morphometric analysis of tissue vascularity in pre-invasive lesi
ons. In addition, we isolated fresh tumors and histologically normal epithe
lium (organoids) from DMBA or vehicle-treated control rats to test their ab
ility to induce endothelial cell tubule formation in vitro. Finally, we exa
mined tumors for their ability to produce vascular endothelial cell growth
factor. The morphometric studies documented that with epithelial progressio
n, the ability of individual cells to elicit angiogenesis increases. The in
vitro studies showed that isolated tumors from these animals stimulate ang
iogenesis. Furthermore, normal epithelium from DMBA-treated rats is more an
giogenic than epithelium from control animals. Finally, DMBA-induced tumors
produce vascular endothelial growth factor (VEGF) mRNA, therefore, DMBA-in
duced mammary tumorigenesis is one model in which to test the dependency of
progression on angiogenesis.